COMBINATION THERAPY OF SUBSTITUTED OXAZOLIDINONES

• US 20100120718A1
• Filed: 10/19/2007
• Published: 05/13/2010
• Est. Priority Date: 11/02/2006
• Status: Abandoned Application

• Current Assignee: Bayer Intellectual Property GmbH (Bayer AG)
• Original Assignee: Bayer Schering Pharma AG (Bayer AG)
• Inventors: Perzborn, Elisabeth
• Application Number:
  US12/513,363
• Publication Number:
  US 20100120718A1
• Time in Patent Office: Days
• US Class Current: 514/81
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/4365 the heterocyclic ring system having sulfur as a ring hetero atom, e.g. ticlopidine
• CPC Class Codes: A61K 31/52 Purines, e.g. adenine
• CPC Class Codes: A61K 31/5377 not condensed and containing further heterocyclic rings, e.g. timolol
• CPC Class Codes: A61K 31/60 Salicylic acid; Derivatives thereof
• CPC Class Codes: A61K 31/616 by carboxylic acids, e.g. acetylsalicylic acid
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 7/06 Antianaemics
• CPC Class Codes: A61P 7/08 Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock artificial tears A61P27/04
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/04 Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Abstract

The present invention relates to combinations of A) oxazolidinones of the formula (I) with B) acetylsalicylic acid (aspirin) and C) an ADP receptor antagonist, in particular P₂Y₁₂ purinoreceptor blocker, to a process for producing these combinations and to the use thereof as medicaments, in particular for the prophylaxis and/or treatment of thromboembolic disorders.

Claims

1. A combination comprising

A) a compound of the formula (I)

in which

R¹ is 2-thiophene which is substituted in position 5 by a radical from the group of chlorine, bromine, methyl or trifluoromethyl,

R² is D-A-:

where;

the radical “

A”

is phenylene;

the radical “

D”

is a saturated 5- or 6-membered heterocycle which is linked via a nitrogen atom to “

A”

,

which has a carbonyl group in direct vicinity to the linking nitrogen atom, and

in which a ring carbon member may be replaced by a heteroatom from the series S, N and O;

where

the group “

A”

defined above may optionally be substituted once or twice in the meta position relative to the linkage to the oxazolidinone by a radical from the group of fluorine, chlorine, nitro, amino, trifluoromethyl, methyl or cyano,

R³, R⁴, R⁵, R⁶, R⁷ and R⁸ are hydrogen,

the pharmaceutically acceptable salts, hydrates, prodrugs thereof or mixtures thereof

B) acetylsalicylic acid

and

C) an ADP receptor antagonist.

2. The combination as claimed in claim 1, characterized in that the compound A) is 5-chloro-N-({(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)phenyl]-1,3-oxazolidin-5-yl}methyl)-2-thiophenecarboxamide of the formula

its pharmaceutically acceptable salts, hydrates, prodrugs or mixtures thereof.

3. The combination as claimed in claim 1, characterized in that the ADP receptor antagonist is a P₂Y₁₂ purinoreceptor blocker.

4. The combination as claimed in claim 3, characterized in that the P₂Y₁₂ purinoreceptor blocker is clopidogrel, prasugrel or cangrelor.

5. The combination as claimed in claim 3, characterized in that the P₂Y₁₂ purinoreceptor blocker is clopidogrel.

6. A process for producing a combination as claimed in claim 1, characterized in that an oxazolidinone of the formula (I), acetylsalicylic acid and an ADP receptor antagonist are combined or prepared in a suitable way.

7. A combination as claimed in any of claim 1 for the prophylaxis and/or treatment of disorders.

8. A pharmaceutical composition comprising a combination as claimed in claim 1 further comprising one or more active pharmaceutical agents.

9. A pharmaceutical composition comprising a combination as claimed in claim 1 and one or more pharmacologically suitable excipients and/or carriers.

10. The use of a combination of claim 1 for producing a pharmaceutical composition for the prophylaxis and/or treatment of thromboembolic disorders.

11. The use of a combination of claim 1 for producing a pharmaceutical composition for the prophylaxis and/or treatment of myocardial infarction with ST segment elevation (STEMI) and without ST segment elevation (non-STEMI), stable angina pectoris, unstable angina pectoris, reocclusions and restenoses following coronary interventions such as angioplasty or aortocoronary bypass, peripheral arterial occlusive diseases, pulmonary embolisms, deep vein thromboses and renal vein thromboses, transient ischemic attacks, and thrombotic and thromboembolic stroke.

12. A method for treating a condition comprising administering a therapeutically effective amount of the combination of claim 1.

13. The method of claim 12 wherein the condition is a myocardial infarction with ST segment elevation (STEMI) and without ST segment elevation (non-STEMI), stable angina pectoris, unstable angina pectoris, reocclusions and restenoses following coronary interventions, peripheral arterial occlusive diseases, pulmonary embolisms, deep vein thromboses and renal vein thromboses, transient ischemic attacks, or thrombotic and thromboembolic stroke.